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Cell Sorting and Cancer Diagnosis Group

We are developing point-of-care devices using microfluidic technologies for capturing circulating tumor cells from peripheral blood of cancer patients. These cells, called circulating tumor cells (“CTCs”), provide a cellular link between the primary malignant tumor and the metastatic sites, and thus, the ability to non-invasively isolate CTCs from the blood of cancer patients has far-reaching diagnostic, prognostic, therapeutic, and basic cancer biology implications. The major challenge for such isolation stems from the fact that, CTCs are very rare in patients with cancer, comprising as few as only 1 to 10 cells/mL of blood, beyond the limits of current cell separation technologies. Recently, we have developed a novel microfluidic platform capable of selective separation of CTCs from the peripheral blood of cancer patients. Using this technology, we successfully demonstrated the capture of CTCs from patients with lung, prostate, colon or pancreatic tumors. This technological advance has important clinical implications and ultimately could be applied as a point-of-care high-throughput diagnostic device and for longitudinal follow-up of cancer patients for tailored targeted therapy.

Examples of ongoing projects include:

  • Isolation of CTCs by utilizing inertial focusing and magnetic selection
  • Capturing CTCs in microvortex generating herringbone chip
  • Microfluidic system for monitoring infection by radio-labeling leukocytes
  • Protein isolation from whole blood using microfluidics

 

Representative Publications:

  • Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, Rothenberg SM, Shah AM, Smas ME, Korir GK, Floyd FP, Gilman AJ, Lord JB, Winokur D, Springer S, Irimia D, Nagrath S, Sequist LV, Lee RJ, Isselbacher KJ, Maheswaran S, Haber DA, Toner M., Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proceedings of the National Academy of Sciences 2010; 107 (43): 18392–18397
  • Stott SL, Lee RJ, Nagrath S, Yu M, Miyamoto DT, Ulkus L, Inserra EJ, Ulman M, Springer S, Nakamura Z, Moore AL,Tsukrov DI, Kempner ME, Dahl DM, Wu CL, Iafrate AJ, Smith MR, Tompkins RG, Sequist LV, Toner M, Haber DA, Maheswaran S. Isolation and characterization of circulating tumor cells from patients with localized metastatic prostate cancer. Science and Translational Medicine 2010; 2(25): 25ra23.
  • DiCarlo D, Edd JF, Humphry KJ, Stone HA, Toner M. Particle segregation and dynamics in confined flows. Physical Review Letters 2009; 102(9): 94503.
  • Maheswaran S, Sequist L, Nagrath S, Ulkus L, Brannigan B, Collura C, Inserra E, Diederichs S, Iafrate J, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins R, Lynch T, Toner M, Haber D. Detection of mutations in EGFR in circulating lung-cancer cells. New England Journal of Medicine 2008; 359: 366-377.
  • DiCarlo D, Irimia D, Tompkins RG, Toner M. Continuous inertial focusing, ordering, and separation of particles in microchannels.  Proceedings of the National Academy of Sciences 2007; 104(48): 18892-1889.
  • Nagrath S, Sequist L, Bell DW, Irimia D, Ulkus L, Maheswaran S, Smith MR, Kwak EL, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M. Microchip-based isolation of rare circulating epithelial cells in patients with metastatic cancer. Nature 2007; 450(7173): 1235-1239.



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